OBJECTIVE: We evaluated prenatal factors related to perinatal loss in twins, using medical records and death certificates, to determine the main perinatal event that contributed to babies' deaths.DESIGN: This was a retrospective cohort study of 550 monochorionic diamniotic or diamniotic dichorionic twins who were delivered at Kaiser Permanente Colorado between 1994 and 2001.MAIN OUTCOME: The main outcome of the study was perinatal loss (stillbirth or neonatal death).OUTCOMES MEASURES: Select maternal risk factors (maternal age, race, marital status, assisted conception, past history of preterm birth, cigarette smoking, and placentation) were included in the univariable and multivariable logistic regression analysis. Data on these risk factors came from review of records from our multiple-birth perinatal database. A comprehensive review of clinical events recorded in the medical records and on the death certificate was conducted to assess the main event that contributed to the loss.RESULTS: In the cohort of 1100 babies, there were 12 stillbirths and 34 neonatal deaths, with an overall frequency of perinatal loss of 4.2%. We found a strong association between a monochorionic diamniotic placentation and perinatal loss (adjusted odds ratio, 3.9; 95% confidence interval, 2, 7.7). At delivery, placental pathology and spontaneous preterm birth accounted for 36% and 41%, respectively, of the clinical events contributing to the demises. Compared with the medical record, review of death certificate information did not contribute significantly to the understanding of the sequence of perinatal events leading to the demise.CONCLUSIONS: We conclude that loss in twins is most strongly associated with monochorionic diamniotic placentation. Although this condition is not preventable, early identification (by ultrasound) and referral to subspecialists may decrease the chances of perinatal loss. Prevention of spontaneous preterm birth in all women remains an important initiative in obstetric care to reduce perinatal mortality and neonatal morbidity. We believe that improvements in the reporting on death certificates will allow future research on large data sets and may provide further insight into perinatal loss in twins. We emphasize the importance of a comprehensive clinical review of each case of perinatal loss to fully understand the sequence of clinical events leading to this adverse pregnancy outcome.